Document Detail

Adenoviral-mediated gene transfer induces sustained pericardial VEGF expression in dogs: effect on myocardial angiogenesis.
MedLine Citation:
PMID:  10690306     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Angiogenic peptides like VEGF (vascular endothelial growth factor) and bFGF (basic fibroblast growth factor) have entered clinical trials for coronary artery disease. Attempts are being made to devise clinically relevant means of delivery and to effect site-specific delivery of these peptides to the cardiac tissue, in order to limit systemic side-effects. We characterized the response of the pericardium to delivery of a replication-deficient adenovirus carrying the cDNA for AdCMV.VEGF165, and assessed the effect of pericardial VEGF165 on myocardial collateral development in a canine model of progressive coronary occlusion. METHODS: Ameroid constrictors were placed on the proximal left circumflex coronary artery of mongrel dogs. Ten days later, 6 x 10(9) pfu AdCMV.VEGF165 (n = 9). AdRSV.beta-gal (n = 9), or saline (n = 7) were injected through an indwelling pericardial catheter. Transfection efficiency was assessed by X-gal staining. Pericardial and serum VEGF levels were measured serially by ELISA. Maximal myocardial collateral perfusion was quantified with radiolabeled or fluorescent microspheres 28 days after treatment. RESULTS: In AdRSV.beta-gal-treated dogs, there was extensive beta-gal staining in the pericardium and epicardium, with minimal beta-gal staining in the mid-myocardium and endocardium. Pericardial delivery of AdCMV.VEGF165 resulted in sustained (8-14 day) pericardial transgene expression, with VEGF levels peaking 3 days after infection (> 200 ng/ml) and decreasing thereafter. There was no detectable increase in serum VEGF levels. Maximal collateral perfusion, a principal correlate of collateral development and angiogenesis, was equivalent in all groups. CONCLUSION: Adenoviral-mediated gene transfer is capable of inducing sustained VEGF165 expression in the pericardium; however, locally targeted pericardial VEGF delivery failed to improve myocardial collateral perfusion in this model.
D F Lazarous; M Shou; J A Stiber; E Hodge; V Thirumurti; L Gonçalves; E F Unger
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cardiovascular research     Volume:  44     ISSN:  0008-6363     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  1999 Nov 
Date Detail:
Created Date:  2000-03-14     Completed Date:  2000-03-14     Revised Date:  2007-05-02    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  294-302     Citation Subset:  IM    
Experimental Physiology and Pharmacology Section, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
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MeSH Terms
Adenoviridae / genetics*
Coronary Disease / metabolism,  therapy*
Endothelial Growth Factors / analysis,  blood,  genetics*
Feces / virology
Gene Expression
Gene Therapy / adverse effects,  methods*
Gene Transfer Techniques
Genetic Markers
Genetic Vectors / administration & dosage*
Lymphokines / analysis,  blood,  genetics*
Neovascularization, Physiologic
Pericardial Effusion / etiology
Pericardium / chemistry,  metabolism*,  virology
Time Factors
Urine / virology
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
beta-Galactosidase / genetics
Reg. No./Substance:
0/Endothelial Growth Factors; 0/Genetic Markers; 0/Lymphokines; 0/VEGFA protein, human; 0/Vascular Endothelial Growth Factor A; 0/Vascular Endothelial Growth Factors; EC

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